tbuckley/cabot-search huggingface dataset:
P11.68.A Hemangiopericytoma, case series and clinic-pathological analysis
Authors: V Redaelli, C Calatozzolo, G Marucci, V Pinzi, P Gaviani, A Botturi, G Simonetti, L Mattei, B Pollo, A Silvani
Journal: Neuro-Oncology (2022)

Abstract Background Hemangiopericytoma (HPC) is an extremely rare aggressive tumor of mesenchymal origin, which constitutes less than 1% of primary tumors of the central nervous system. Typically it occurs in young adults (mean age at diagnosis 30-50 years). Initially described as gemmangiomas, was first called hemangiopericytoma in 1942 but it was considered as a variant of meningioma until 1993 when it was finally recognized as a distinct clinical-pathological entity by the World Health Organization (WHO). In 2016, there was the unification of both HPC and Solitary Fibrous Tumor (SFT) in a single spectrum of rare and thick mesenchymal tumors due to the identification, in both tumoral types, of a molecular alteration called NAB2-STAT6 fusion. Material and Methods The present study is a case series of patients that received a pathological diagnosis of SFT/HPC at our Institute from 1981 to 2020. Clinical data included: demographic data, tumor characteristics and treatment modality. Hystological diagnosis and immunohistochemistry allowed to confirm diagnosis, based on the 2016 WHO classification. Haematoxylin staining was completed with immunohistochemistry with primary antibodies for STAT 6 and evaluation of presence of tumor necrosis. Statistical analysis was conducted considering age at first diagnosis, treatment modality, extent of tumor resection, presence of necrosis in histological analysis compared to PFS-1, OS and relapses number. Results The case series was composed by 82 patients (46 men and 36 women) with median age of 43 (± 20) that accede to our Institute from 1981 to 2020. Our statistical analysis showed significative correlation between age, extend of tumor resection and presence of necrosis with OS and relapses number. Conclusion Hemangiopericytoma is a very rare cerebral tumors, and for this reason large case series are not disposable in literature. In our study we collected all disposable data of every patient with pathological diagnosis of SFT/HPC acceded to our hospital in the long period of 39 years in the aim to verify the presence of significative correlations. We observed strong correlation between tumor resection and presence of necrosis in tumor tissue with prognosis parameters (OS and number of relapses). This result it could be important to conduct the decisional process about treatment after surgical resection, considering also pathological features, rather than only surgical resection.
P01.06.B Interim results from CAR-Study B: An ongoing randomized trial on the effect of SRS or WBRT on cognitive performance in patients with 11-20 brain metastases
Authors: W C M Schimmel, E Verhaak, P E J Hanssens, X M Kavelaars, J Mulder, M C Kaptein, M M Sitskoorn, K Gehring
Journal: Neuro-Oncology (2022)

Abstract Background Both stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) have proven to be effective treatments for multiple brain metastases (BM) with similar overall survival. Cognition and Radiation (CAR) Study B is a randomized trial on the effect of Gamma Knife radiosurgery (GKRS) or WBRT on cognitive performance in patients with 11-20 BM. The primary and secondary aim of this interim analysis were to check whether Bayesian stopping rules for cognitive failure were met, and to compare cognitive changes after treatment respectively, for the first 45 patients enrolled. Material and Methods Patients with 11-20 newly diagnosed BM on a triple-dose contrast-enhanced MRI-scan, expected survival &amp;gt;3 months and Karnofsky Performance Status (KPS) ≥70, were stratified by age, histology, total BM volume, systemic treatment, KPS, and baseline Hopkins Verbal Learning total recall (HVLT-R TR) score, and randomized 1:1 (minimization) to GKRS or WBRT. Neuropsychological tests were administered before (T0) treatment (n=21 vs n=20), and at 3 (T3; n=16 vs n=14) and 6 (T6; n=9 vs n=9) months thereafter. A decline of ≥5 points in HVLT-R TR score was considered a cognitive failure. The trial would be halted if the posterior probability for a higher cognitive failure rate in one group versus the other was &amp;gt;0·975 at T3 or T6 according to the employed beta (2.09,2.91) prior (prior mean of 42%), based on the average failure rates at 4 months reported by Chang et al. (2009). Between-group differences in changes of test performances over 6 months were analyzed using mixed ANOVAs. Proportions of cognitive changes (T0-T6) at the individual level based on reliable change indices correcting for practice effects, were determined. Results HVLT-R TR failure rates in the GKRS versus WBRT group were 31% versus 29% at T3, and 0% versus 33% at T6. The observed failure rates after WBRT at T3 and T6 were lower than the average failure rates of Chang et al. (2009). Posterior probabilities were 0·451 at T3 and 0·918 at T6. Over 6 months, changes in performance on tests of immediate (p=·003) and delayed recall (p=·024), and information processing speed (p=·003) were significantly different between groups (large effect sizes), with significant declines after WBRT, but not after GKRS. Over 6 months, at the individual patient level, there were no declines in performances across all tests in the GKRS group (n=8) while performances declined in 4 out of 8 patients in the WBRT group. Conclusion The stopping rules were not met since the posterior probabilities did not cross the threshold. Other preliminary findings in this small sample suggest that cognitive decline, both at group and individual level, is more pronounced after WBRT compared to GKRS. Accrual is continued (NCT02953717; ZonMw 842003006).
P08.10.B Family-centred care in neuro-oncology: a longitudinal mixed-methods feasibility study
Authors: K Piil, G Locatelli, S Laegaard Skovhus, A Tolver, M Jarden
Journal: Neuro-Oncology (2022)

Abstract Background A diagnosis of a malignant brain tumour represents a fearful event for patients, often followed by severe physical, cognitive, emotional, and psychosocial impairments. In turn, being a family member and an informal caregiver of a person with an oncological disease is also a burdensome experience. Family and network can influence patient outcomes, and family-centred intervention may help both patients and caregivers to face illness-related issues. However, studies aiming at implementing family-centered interventions in patients with high grade glioma (HGG) and their families are scarce. Therefore, this study aims to understand how patients with HGG and their families experienced the course of illness and investigate the impact of family and network consultations (FNCs) on both of them. Material and Methods We adopted a quasi-experimental feasibility study using a longitudinal mixed-methods design. The intervention consisted of three FNCs delivered over a 1-year period. Quantitative data on physical activity level, anxiety, depression, family functioning, perceived nursing support, symptom burden and interference on daily living, caregiver burden and quality of life were collected at four time points. Qualitative data on patients’ and families’ perspectives on the intervention were explored through telephone interviews. Results A total of 21 patients with HGG and 47 family members were included in the study. Patients mean age was 66 years and they were mainly male (86%), married and living with the patient (95%), and retired (54%). Caregivers mean age was 47 years, and they were mainly female (62%), children of the cared person (47%), and employed (55%). The integration of quantitative and qualitative data showed that many variables improved over time (e.g., symptom interference in patients, family functioning in caregivers, quality of life) or remained stable (e.g., anxiety and depression), apart from physical functioning and symptom burden that worsened. Families described FNCs as a valuable strategy to holistically address the needs and concerns of the entire family and to strengthen the family dialogue and union. Conclusion FNCs can be a valuable strategy to implement family-centred care practices. However, advanced nursing competencies are required to provide optimal family-centred care. Plus, the intervention should be personalized and based on the needs of each family.
P11.40.A Clinicopathological Analysis of High risk Pituitary Adenomas According to the 2017 WHO Classification System for Pituitary Neuroendocrine Tumors (PitNET)
Authors: Y Kim, S Ahn, S Jeun, Y Lee, J Park
Journal: Neuro-Oncology (2022)

Abstract Background The 2017 WHO classification of pituitary tumors has revealed “high-risk pituitary neuroendocrine tumors (PitNETs)”, which were known to have high probability for recurrence. Tumor invasion was not included in the pathological grading and classification due to frequent lack of proper pathologic assessment. However, it mentioned tumor invasion as an important prognostic feature in identifying clinically aggressive adenomas. Material and Methods We performed a retrospective review of a prospectively collected dataset from January 2018 to March 2021. Patient’s clinical presentation, radiologic features, pathologic findings, and clinical outcome were gathered. Inter-group analysis was performed for high-risk versus low-risk tumors, and invasive versus non-invasive tumors. Results Among total 116 cases of PitNETs, high-risk and low-risk tumors were identified in 32 and 84 cases, respectively. The inter-group comparison showed no differences in clinical presentation, radiologic features, pathologic findings, and clinical outcomes.Invasive and non-invasive tumors were identified in 49 and 67 cases, respectively. The invasive group tumors were more symptomatic ( 29 (59.2%) vs. 30 (44.8%), p= 0.031), with larger tumor size over 40mm (9 (18.4%) vs. 1 (1.5%), p = 0.002), and more likely to have Knosp grade higher than 3. The gross-total resection was less achievable (7 (14.3%) vs 26 (38.8%), p = 0.007) However, Ki-67 index showed no significantly difference between the invasive group and non-invasive group (2.0 vs 2.0 , p= 0.556). Conclusion According to our study results, the pathologic diagnosis of a high-risk tumor does not necessarily seem to properly reflect the clinical aggressiveness. Tumor invasion, however, seems to better represent the aggressive tumors that requires proper and active treatment.
P03.06.B Proton irradiation (PT) for benign meningiomas, Grade I clinical experience of the first 100 patients from REGI-MA-002015
Authors: C Lütgendorf-Caucig, E Hug, M Pelak, B Flechl, U Mock, P Fossati, M Mumot, A Carlino, P Georg, P Georg
Journal: Neuro-Oncology (2022)

Abstract Background Meningiomas are the most common CNS tumors and the majority is regarded as benign. However, a subset of patients presents with complex tumors involving several anatomic compartments of the skull base - eluding any concepts of gross total resection. Proton therapy (PT) is applied as definitive treatment for primary or recurrent disease or postoperatively following subtotal resection. We report on the first 100 adult patients treated with PT at MedAustron. Material and Methods All patients were enrolled in a prospective registry trial (ClinicalTrials.gov Identifier: NCT03049072). Target volume definition was based on CT, MR and DOTA-PET/CT. PT treatment plans were generated by applying a Simultaneous Integrated Boost (SIB) concept with the Single Field-optimisation method and utilizing 2-4 beams per plan with a beam spacing of &amp;gt;30°. Prescribed doses to PTV1 were 50.49Gy_RBE at 1.87Gy_RBE/fr and 54.0Gy_RBE at 2.0Gy_RBE/fr to PTV2 in overall 27 fractions. Follow up status was assessed by MRI at 6, 12 months and annually thereafter, side effects were assessed using CTCAE v4.0. and quality of life (QoL) using EORTC-CTC30 and BN20 questionnaires. The scores entered by the patients were added and normalized to 0-100 scale according to previously described protocols. Results Between 08/2017 and 04/2021, 100 patients were treated, 22% (n=22) male and 78% (n=78) female patients. Median age at therapy was 54a (25a-82a). In 57% (n=57) PT was the definitive treatment (no resection or surgery &amp;gt;12 mo prior to PT). 43% (n=43) underwent postoperative PT with at least one surgery (range 1-3), and median time from last resection to start of PT of 6mo (3mo-11mo). 89% (n=89) meningiomas were located in the skull base with involvement of multiple anatomic compartments. The median GTV size was 24cc (1cc-226cc) and the median CTV 41cc (2cc-352cc), respectively. At median follow-up of 31.1 months (range 6.6-51.6), 2 local in-field failures were observed (both patients treated postoperatively) resulting in disease-specific survival of 100% and local control of 98% at 3 years, respectively. No &amp;gt; Grade 2 acute toxicity was observed. During follow-up two Grade 3 toxicities occurred: One patient developed symptomatic radiation induced brain lesion (RIBL) which resolved within 12 month; one patient was hospitalized for new onset of epilepsy without corresponding radiographic findings. 9% (n=9) developed G1/G2 RIBL, which resolved spontaneously. The general QoL including the global health status and all functioning domains remained stable and did not decrease significantly following PT. Conclusion First clinical data demonstrate that PT based on a SIB concept is a safe and efficient treatment of anatomically complex, low grade meningiomas. Acute and late toxicity incidences in our series were low with excellent, prospectively assessed preservation of QoL.
P11.72.A Glioblastoma in elderly patients. Which is the best treatment option?
Authors: C A Costa, M Sousa, M R Pires, J C Monteiro, A Caetano, S Póvoa, A Pêgo, G Sousa
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, and it is associated with a poor prognosis in the elderly. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). In elderly patients with GBM, short-courses of radiotherapy with TMZ are used. Material and Methods We performed a single-center retrospective analysis of elderly GBM patients treated from 2013 to 2020. The primary endpoint was to evaluate progression free survival (PFS) and overall survival (OS) according to treatment received (TMZ and standard radiotherapy (60 Gy over a period of 6 weeks) vs TMZ and short-course radiotherapy (40 Gy in 15 fractions)). Secondary endpoints were analysis of population demographics and major toxicities associated to treatment. Results Twenty-two patients were identified. The median age was 72 years (range 65- 80), 18 (85.7%) patients were in ECOG-PS 0-1, 12 (57.1%) were males and all patients had undergone partial or complete resection surgery. Eleven (52.4%) patients received TMZ and standard radiotherapy and 10 (47.6%) patients received TMZ and short-course radiotherapy. Three (14.3%) patients had complete remission, 11 (52.4%) patients had partial response, 2 (9.5%) patients presented stable disease and 5 (23.8%) patients had disease progression. Median OS was 9 months (95% CI, 3.6 to 14.4) with TMZ with standard radiotherapy and 8 months (95% CI, 1.8 to 14.2) with TMZ and short-course radiotherapy (p=0.322). Median PFS was 5 months (95% CI, 2.8 to 7.2) with TMZ with standard radiotherapy and 6 months (95% CI, 3.1 to 8.9) with TMZ and short-course radiotherapy (p=0.944). Most common toxicities were hematological, with 5 (23.8%) patients presented thrombocytopenia grade 2 or higher. Five (23.8%) patients presented grade 3/4 toxicities (2 (9.5%) patients presented thrombocytopenia grade 4, 1 (4.8%) patient presented thrombocytopenia grade 3, and 2 (9.5%) patients presented anemia grade 3. Conclusion The prognosis of GBM remains poor besides standard therapy. TMZ and short-course radiotherapy should be an option in elderly patients due to its non-inferiority. Elderly patients should undergo a careful geriatric evaluation before starting treatment.
P11.39.B An unusual case of astroblastoma in adult: a case report and review of the literature
Authors: L d Bernardes, A José Santos, G Novaes de Rezende Batistella, M Silva Catito, A Martini Pazini, T Neri Andrade, B Gutierres Gambirasio, N Silva Fernandes, L Henriques Coronatto, I Caroline Freitas Barboza
Journal: Neuro-Oncology (2022)

Abstract Background Astroblastoma is an uncommon glial neoplasm of controversial histogenesis, clinical behavior and response to treatment yet to be understood. It usually appears in the cerebral hemisphere of young patients, preferably in the frontal and parietal lobes. Histologically, its characteristics overlap with high-grade gliomas, making the differential diagnosis between these entities complex. Clinical, radiological, histopathological correlations and, if necessary, genetic tests (MN1 Rearrangement) are essential for an accurate diagnosis. Material and Methods We present a case report based on data collected retrospectively from electronic medical records. Results A 63-year-old male with a 3-month history of headache and one episode of mental confusion. In the neurological exam, language alteration was noted and the other systemic exams were normal. Magnetic resonance imaging of the brain revealed an intra-axial expansive formation involving the insula, superior and middle temporal gyrus, left portion of brainstem, with lobulated contours and heterogeneous, solid-cystic appearance with intermingled hematic foci. The solid portion had heterogeneous contrast enhancement and foci of gross calcification. The lesion was resected and the postoperative MRI showed no residual tumor lesion. Histopathological evaluation showed an extensive pattern of perivascular pseudorosettes of astrocytic cells with broad processes radiating to central vessels, in addition to frequent foci of hyalinization. Immunohistochemistry showed positive staining with antibodies to glial fibrillary acidic protein (GFAP), vimentin and S100 protein, in addition to membranous positivity for epithelial membrane antigen (EMA). The Ki-67 index was 20%. Based on these data, the diagnosis of NOS astroblastoma was established. Four months after resection, imaging follow-up displayed enhancement of the surgical cavity, suggestive of local recurrence. The patient underwent three-dimensional conformal radiotherapy with a total dose of 6000cGy in 30 sessions, followed by adjuvant chemotherapy with temozolomide.The patient did not have tumor recurrence until the last follow-up made 16 months after surgery. Conclusion This is an atypical case of an extremely rare glial tumor of the central nervous system, since most patients with astroblastoma range from 3 months to 40 years (median: 15 years), which makes the diagnosis challenging.
P18.04.A Cay10603, HDAC6 inhibitor, enhances radiosensitivity in meningioma via supressing the nuclear beta-catenin accumulation
Authors: J Na, R Laney, C Hanemann
Journal: Neuro-Oncology (2022)

Abstract Background Meningioma is the most frequent primary central nervous system tumour (PCNST) which account ca 36% of all PCNST. Due to the lack of efficient chemotherapy for meningioma, radiotherapy often become a first-line treatment especially when the tumour is not operable. Radiotherapy plays a crucial role in local control but its efficacy is restricted by radioresistance and by normal tissue radiation tolerance. Therefore, developing and evaluating potential radiosensitisers to enhance therapeutic efficacy are needed.Histone deacetylase (HDACs) expression is generally increased in many cancer types and regulate the expression of numerous proteins involved in tumorigenesis. Targeting HDAC using HDAC inhibitor (HDACi) represent promising radiosensitisers that affect various biological processes, such as cell survival, apoptosis, and DNA repair. Material and Methods We investigated whether pre-treatment with the hydroxamate-based HDAC6 inhibitor, Cay10603, impacts radiation-induced DNA double-strand break (DSB) induction, cell survival, cell cycle arrest, and cell death using immunocytochemistry, clonogenic assay, and flow cytometry in meningioma cell lines. Low concentration (100 nM) of Cay10603 was treated 24 hr prior to high energy x-ray irradiation (2 Gy) by a medical linear accelerator (LINAC). To investigate the nuclear localisation of beta-catenin, subcellular fractionation and Western Blotting were conducted. Results We found that tumour cells survival was synergistically decreased after combination treatment of Cay10603 and radiation. Combination therapy induced DNA damage with activation of histone gH2AX and increased G2/M arrest compared to drug or radiation alone. Both apoptotic and necrotic cell death were increased after combination therapy. To focus on the mechanisms of action of HDAC6 inhibition followed by radiation, we further investigated nuclear localisation of beta-catenin levels. The results showed the both beta-catenin and c-myc expression in the nucleus was suppressed after combination therapy. Conclusion In meningioma cells, radiotherapy in combination with HDAC6 inhibitor reduces the nuclear localisation of beta-catenin and synergistically decreases cell survival. Our findings demonstrate a potential therapeutic strategy of Cay10603 to improve the radiosensitisation for meningioma cells.
P10.10.A Tumor Treating Fields (TTFields), temozolomide and lomustine co-application is efficacious in glioblastoma cancer cell lines
Authors: H Fishman, R Monin, E Dor-On, C Wolfbauer, A Haber, M Giladi, U Weinberg, Y Palti
Journal: Neuro-Oncology (2022)

Abstract Background Temozolomide (TMZ) is the standard of care chemotherapy for newly diagnosed glioblastoma (ndGBM), the most common primary malignant brain tumor in adults. However, 50% of patients do not respond to TMZ due to expression of O6-methylguanine-DNA methyltransferase (MGMT), the enzyme involved in repair of TMZ-induced damage. Tumor Treating Fields (TTFields) are alternating electric fields that display anti-mitotic effects on cancerous cells, and have been shown to induce a state of BRCAness in various cancer types. Concurrent treatment with TMZ and TTFields demonstrated a major advance in treatment of patients with ndGBM, and was approved by the FDA in 2014. Recently, the addition of lomustine (CCNU) to TMZ demonstrated clinical benefit in ndGBM patients, with improved overall and progression free survival. The aim of the current study was to examine in GBM cells the effect of TTFields in conjunction with TMZ and CCNU. Materials and Methods U-87 MG, LN229, U118 and LN18 human GBM cell lines were tested for their MGMT expression levels, and treated with TTFields (200 kHz, of 0.83 V/cm RMS) for 72 h using the inovitro system. Efficacy of concomitant application of TTFields with TMZ and/or CCNU was tested by measuring cell count, colony formation, and apoptosis levels. Results U-87 MG and LN229 displayed no expression of MGMT, while U118 and LN18 expressed low and high levels of MGMT, respectively. Application of TMZ and TTFields resulted in increased cytotoxicity compared with each treatment alone, with an additive interaction seen in all examined cell lines. The cytotoxic effect resulting from co-application of CCNU with TTFields suggested a synergistic interaction between the two modalities for U-87 MG, LN229, and U118, an additivity for LN18. Concurrent TTFields/TMZ/CCNU was more efficacious than TTFields or TMZ/CCNU separately in all cell lines. Conclusions Application of TTFields with TMZ was additive, irrespective of MGMT expression levels, while TTFields with CCNU was additive when MGMT was plentiful, but displayed tendency to synergism when MGMT was absent or limited. These outcomes are in line with the BRCAness state induced by TTFields, as in the absence of MGMT, DNA damage induced by CCNU requires the BRCA pathway for repair. Application of TTFields together with TMZ and CCNU demonstrated increased efficacy, suggesting potential benefit of such therapy for ndGBM treatment.